[논문]Platycodin D enhances LDLR expression and LDL uptake via down-regulation of IDOL mRNA in hepatic cells

Choi, Yu-Jeong; Lee, Sol Ji; Kim, Hyo In; Lee, Hee Jung; Kang, So Jung; Kim, Tai Young; Cheon, Chunhoo; Ko, Seong-Gyu

doi:10.1038/s41598-020-76224-w

[해외논문] Platycodin D enhances LDLR expression and LDL uptake via down-regulation of IDOL mRNA in hepatic cells 원문보기

Scientific reports, v.10 no.1, 2020년, pp.19834 -

Choi, Yu-Jeong (Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447 Republic of Korea) , Lee, Sol Ji (Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447 Republic of Korea) , Kim, Hyo In (Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, 02447 Republic of Korea) , Lee, Hee Jung (Department Global Public Health and Korean Medicine Management, College of Korean Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea) , Kang, So Jung (Department of Clinical Koeran Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea) , Kim, Tai Young (Center for Cognition and Sociality, Institute for Basic Science, Daejeon, 34126 Republic of Korea) , Cheon, Chunhoo (Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul, 130-701 Korea) , Ko, Seong-Gyu (Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi, Seoul, 130-701 Korea)

Abstract ▼ AI-Helper

The root of Platycodon grandiflorum (PG) has long been used as a traditional herbal medicine in Asian country. Platycondin D (PD), triterpenoid saponin that is a main constituent of PG, exhibits various biological activities such as anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer effects. A previous study showed that PD had cholesterol-lowering effects in mice that develop hypercholesterolemia, but the underlying molecular mechanisms have not been elucidated during the last decade. Here, we demonstrated that both PG and PD markedly increased levels of cell surface low-density lipoprotein receptor (LDLR) by down-regulation of the E3 ubiquitin ligase named inducible degrader of the LDLR (IDOL) mRNA, leading to the enhanced uptake of LDL-derived cholesterol (LDL-C) in hepatic cells. Furthermore, cycloheximide chase analysis and in vivo ubiquitination assay revealed that PD increased the half-life of LDLR protein by reducing IDOL-mediated LDLR ubiquitination. Finally, we demonstrated that treatment of HepG2 cells with simvastatin in combination with PG and PD had synergistic effects on the improvement of LDLR expression and LDL-C uptake. Together, these results provide the first molecular evidence for anti-hypercholesterolemic activity of PD and suggest that PD alone or together with statin could be a potential therapeutic option in the treatment of atherosclerotic cardiovascular disease.

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